10 Participants Needed

Nitroglycerin for Migraine

AJ
DJ
Overseen ByDavid J Altschul, MD
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Approved in 3 JurisdictionsThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

Migraine is the most common headache disorder, prevalent in 18% of females and 6% of males. Emergency room visits, physician consults, hospitalizations, medications, and indirect costs such as lost work days and decreased productivity place the global economic burden of migraines at over 20 billion dollars. It is prevalent in 28 million people in the US alone. Symptoms include unilateral, throbbing, debilitating headache pain accompanied by nausea, vomiting, photophobia, and phonophobia. Upwards of 75% of migraine patients have reduced functionability, have lost time at work, and 1/3 of patients require bed rest to manage the symptoms. The health-related impact on quality of life was comparable with that experienced by patients with congestive heart failure, hypertension, or diabetes. While the burden of migraines on our society is clear, the pathophysiology of migraines remains largely unknown. The trigeminovascular system, including the external and internal carotid arteries and their associated sensory fibers which subserve the head have long been implicated in the pain and cutaneous allodynia experienced by migraine patients. Wolff in 1953, was the first to posit that migraine headache pain is the caused by dilation or circumferential expansion of the extracranial carotid artery. He demonstrated that migraineurs had twice the pulse amplitude in their external carotid arteries compared to control subjects and these changes were directly correlated to migraine symptoms. In a 2008 study, randomized migraineurs received nitroglycerin via peripheral IV or placebo for 20 minutes prior to obtaining magnetic resonance angiography (MRA). Nitroglycerin, a potent dilator of blood vessels, reliably induced migraine-like pain in up to 80% of patients, and transient dilation of vessels of up to nearly 40%, mostly in the extracranial vessels. Sumatriptan's efficacy in migraine relief provides further evidence for this theory, as it is a selective extracranial vessel constrictor which does not cross the blood brain barrier. The goal of this current work is to utilize the direct, real-time angiography, which provides a high resolution map of vasculature, and demonstrate changes in vessel flow in patients who have migraine headache attacks. This information may guide therapeutic interventions in the future in order to better treat these migraine patients.

Do I need to stop my current medications for the trial?

You may need to stop taking certain medications, especially if they are vasoactive drugs or similar to nitroglycerin. The trial excludes participants taking these types of medications.

Is nitroglycerin generally safe for humans?

Nitroglycerin (also known as glyceryl trinitrate or GTN) can cause headaches in healthy people and trigger migraines in those prone to them. It dilates blood vessels, which is why it can lead to these effects.12345

How does the drug nitroglycerin differ from other migraine treatments?

Nitroglycerin, also known as glyceryl trinitrate, is unique because it is typically used to provoke migraines in research settings rather than treat them. It works by releasing nitric oxide, which can cause headaches and mimic migraine symptoms, making it different from standard migraine treatments that aim to relieve or prevent symptoms.12346

Research Team

David J. Altschul, MD | Montefiore Einstein

David J Altschul, MD

Principal Investigator

Montefiore Medical Center

Eligibility Criteria

This trial is for adults with a neurologist-confirmed diagnosis of migraine, experiencing migraines at least twice a month and not responding to standard treatments. Participants must have had stable neurological exams in the past 6 months and be willing to undergo angiography. Pregnant women, children, those with severe pulmonary or cardiac conditions, recent caffeine or alcohol intake, or on certain medications are excluded.

Inclusion Criteria

You have not had any changes in your neurological exam in the past 6 months.
You have tried regular migraine treatments and still have severe, debilitating symptoms.
You have migraines that are different from other types of headaches.
See 3 more

Exclusion Criteria

Subjects who do not consent to participate
Subjects who are pregnant and children
You have had treatment or surgery on your brain for any brain issues in the past.
See 9 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks
1 visit (in-person)

Pre-Angiography Evaluation

Participants undergo a clinic visit for history and physical evaluation, and complete a migraine questionnaire and headache log

1 day
1 visit (in-person)

Angiography and Immediate Post-Procedure Monitoring

Participants undergo angiography with nitroglycerin administration and vessel occlusion testing, followed by a 5-hour monitoring period

1 day
1 visit (in-person)

Follow-up

Participants complete a headache log and are monitored for migraine frequency and therapies utilized for 2 weeks post-angiogram

2 weeks
1 visit (in-person)

Treatment Details

Interventions

  • Nitroglycerin
Trial Overview The study aims to understand migraine pain by using nitroglycerin-induced dilation of blood vessels during an angiogram to simulate migraine symptoms. Researchers will observe changes in vessel flow during headache attacks which could inform future treatment strategies.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Migraine InterventionExperimental Treatment1 Intervention
Subjects who will be administered 200 micrograms of nitroglycerin once into branches of their external carotid artery to determine the role of dilation of this artery to cause migraine-like pain

Find a Clinic Near You

Who Is Running the Clinical Trial?

Montefiore Medical Center

Lead Sponsor

Trials
468
Recruited
599,000+

Findings from Research

The pharmaceutical industry is losing interest in developing migraine drugs, partly due to the absence of reliable animal models for testing these medications.
The infusion of glyceryl trinitrate (GTN) is recognized as the most validated human migraine model, and efforts have been made to adapt this model for use in animals, highlighting the need for effective testing methods.
Towards a reliable animal model of migraine.Olesen, J., Jansen-Olesen, I.[2013]
Using a clinically relevant dose of glyceryl trinitrate (GTN) in awake rats, researchers successfully simulated a migraine model, showing significant upregulation of the nociceptive marker c-fos in the trigeminal nucleus, which is associated with migraine pain.
The model's specificity for migraine was confirmed by the attenuation of c-fos activation with sumatriptan, a common migraine treatment, making it a valuable tool for testing new anti-migraine drugs.
A naturalistic glyceryl trinitrate infusion migraine model in the rat.Ramachandran, R., Bhatt, DK., Ploug, KB., et al.[2013]
Infusion of glyceryl trinitrate (GTN) in rats led to significant transcriptional changes in the trigeminal ganglia, with 15 genes showing altered expression, indicating a biological response to the treatment.
The analysis revealed pathways related to immune response, signal transduction, and neuroplasticity, suggesting that GTN infusion may activate mechanisms relevant to migraine development and could help in understanding migraine pathogenesis.
RNA Sequencing of Trigeminal Ganglia in Rattus Norvegicus after Glyceryl Trinitrate Infusion with Relevance to Migraine.Hougaard Pedersen, S., Maretty, L., Ramachandran, R., et al.[2023]

References

Towards a reliable animal model of migraine. [2013]
A naturalistic glyceryl trinitrate infusion migraine model in the rat. [2013]
RNA Sequencing of Trigeminal Ganglia in Rattus Norvegicus after Glyceryl Trinitrate Infusion with Relevance to Migraine. [2023]
Prednisolone reduces nitric oxide-induced migraine. [2015]
Delayed migraine-like headache in healthy volunteers after a combination of acetazolamide and glyceryl trinitrate. [2016]
Infusion of low dose glyceryl trinitrate has no consistent effect on burrowing behavior, running wheel activity and light sensitivity in female rats. [2017]